atovaquone

Inhibiting TDP43 expression or using our newly identified TDP43 inhibitor, atovaquone, suppresses OXPHOS and reduces EGFR-TKI resistance. Overall, our research identified TDP43 as a key regulator of EGFR-TKI sensitivity and resistance, and offers new therapeutic targets and promising application perspectives in TNBC.

Data from this study provides a mechanistic basis for PD-L1 elevation in tumors treated with atovaquone. Our studies support further development of atovaquone-anti-PD-L1 combination for the treatment of ovarian and other malignancies.

Furthermore, it predicted 51 candidate therapeutants, including atorvastatin, GSK-269962A, and atovaquone. These findings indicate that even in the absence of overt pathological stimulation, aortic tissue carrying the Myh11 K1256del variant exhibits a transcriptional program centered on ROCK signaling, which may prime the aorta for maladaptive responses to additional stress and may enhance susceptibility to dissection. This computational analysis requires experimental validation, but may provide a hypothesis-generating framework for development of preventive pharmacological interventions against FTAAD.

To address these challenges, we report a multifunctional nano-photosensitizer (TACR) constructed via a one-step self-assembly of a mitochondrial-targeting photosensitizer (TPP-Ppa), the hypoxia-relief agents (catalase and atovaquone), and a tumor-targeting ligand (RGD-PEG-BSA)...TACR-mediated photodynamic therapy induces immunogenic cell death and remodels the tumor microenvironment. In combination with α-PD-L1 immune checkpoint blockade, it elicits a systemic antitumor immune response, effectively suppressing both primary and distant tumors.

The combination of anti-PD-L1 and paclitaxel (PTX) is a standard-of-care regimen for triple-negative breast cancer (TNBC)...This project aims to construct an albumin-based nanomedicine coloaded with atovaquone (ATO) and PTX for targeted tumor delivery, thereby enhancing the therapeutic efficacy of ICBs...This transformative approach significantly enhances the therapeutic efficacy of combination chemotherapy, leading to potent suppression of primary tumors while concurrently preventing postoperative recurrence and pulmonary metastases. This project has the potential to introduce innovative strategies and methodologies aimed at overcoming the limited efficacy of PTX combined with ICBs in the treatment of TNBC.

P1, N=26, Completed, Baylor College of Medicine | Active, not recruiting --> Completed

P4, N=416, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre

We explored the significance of Treg and programmed cell death characteristics in the ccRCC tumor microenvironment and established clinically translatable tools for ccRCC diagnosis, prognosis, and personalized therapy selection, thus promoted the application of explainable machine learning models in precision oncology. Furthermore, We have identified SLC11A1 as a highly promising therapeutic target for ccRCC.

Moreover, increased expression of ligands for activating receptors of NK cells was observed, and coculture experiments revealed enhanced NK cell activity toward atovaquone-treated cells. These results highlight atovaquone's potential to activate immune responses, offering a new avenue for combination therapies in EOC treatment.

P2, N=28, Recruiting, Emory University | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2026

To address these challenges, we developed a multifunctional immunophotothermal nanoplatform (IAC NPs) through rational engineering of human serum albumin for combinatorial delivery of indocyanine green as a photothermal converter, atovaquone for HSP70-mediated thermoresistance blockade, and celecoxib for COX-2/PGE2 pathway inhibition. In vivo, the IAC NPs mediated profound suppression of both primary tumors and metastatic dissemination while exhibiting optimal biocompatibility for clinical translation. Our work validates a nanoenabled self-delivery system that augments the efficacy of LTPTT immunotherapy against TNBC by orchestrating coordinated inhibition of HSPs and inflammatory responses.

Our findings uncover the critical role of MSN in regulating STAT3-mediated cancer stemness via the IL-6/NF-κB signaling axis. These results provide a strong rationale for repositioning STAT3 inhibitors such as Atovaquone as a therapeutic strategy in Adriamycin-resistant TNBC patients exhibiting pSTAT3-MSN complex upregulation.